Key result
CRM1 inhibition alters snRNP interactions with Cajal bodies, suggesting it maintains these trafficking pathways.
Why the study?
The molecular mechanisms maintaining distinct pathways of splicing snRNP trafficking within the mammalian nucleus are not fully understood, particularly the role of CRM1.
The export receptor CRM1 is a key player in the molecular mechanism for maintaining snRNP trafficking pathways in the mammalian nucleus.
Challenges passive diffusion model for nuclear RNP transport; leaves open relevance to cardiovascular gene regulation.
Distinct pathways of ribonucleoprotein transport exist within the nucleus, connected to their biogenesis and maturation. These occur despite evidence that the major mechanism for their movement within the nucleus is passive diffusion. Using fusions of Sm proteins to YFP, CFP and photoactivatable GFP, I have demonstrated that pathways with uni-directional bulk flow of complexes can be maintained within the nucleus despite multi-directional exchange of individual complexes. Newly imported splicing small nuclear ribonucleoproteins (snRNPs) exchange between Cajal bodies (CBs) within a nucleus and access the cytoplasm, but are unable to accumulate in speckles. By contrast, snRNPs at steady-state exchange freely in any direction between CBs and speckles, but cannot leave the nucleus. In addition to these surprising qualitative observations in the behaviour of nuclear complexes, sensitive live-cell microscopy techniques can detect subtle quantitative disturbances in nuclear dynamics before they have had an effect on overall nuclear organization. Inhibition of the nuclear export factor, CRM1, using leptomycin B results in a change in the dynamics of interaction of newly imported snRNPs with CBs. Together with the detection of interactions of CRM1 with Sm proteins and the survival of motor neurons (SMN) protein, these studies suggest that the export receptor CRM1 is a key player in the molecular mechanism for maintaining these pathways. Its role in snRNP trafficking, however, appears to be distinct from its previously identified role in small nucleolar RNP (snoRNP) maturation.
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Judith Sleeman (2007) studied snRNP trafficking in mammalian nucleus. Leptomycin B (CRM1 inhibition) was evaluated on Dynamics of interaction of newly imported snRNPs with Cajal bodies. Inhibition of the nuclear export factor CRM1 using leptomycin B altered the dynamics of interaction of newly imported snRNPs with Cajal bodies, suggesting CRM1 maintains these trafficking pathways.
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